Alpha-mangostin decreased cellular senescence in human umbilical vein endothelial cells.

Abstract

The hyperglycemic condition in diabetes induces cellular senescence in vascular endothelial cells and causes cardiovascular complications. Alpha-mangostin is a xanthone found in Garcinia mangostana, and has shown protective effects in metabolic syndrome. In this study, the anti-senescence effects of alpha-mangostin in the hyperglycemic condition are investigated. HUVECs were incubated with high glucose for 6days and co-treated by metformin or alpha-mangostin. After 6days, cell viability, reactive oxygen species, the percentage of senescent cells, secretory interleukin-6, and the expression of SIRT1, AMPK, p53 and p21 were measured. High glucose (60mM) significantly decreased cellular viability and increased reactive oxygen species and cellular senescence through the reduction of senescence-associated β-galactosidase activity. Moreover, high glucose increased the protein levels of p53, acetyl-p53 and p21. The protein levels of SIRT1 and total AMPK were decreased by high glucose. High glucose increased the secretion of IL-6. Alpha-mangostin (1.25μM) and metformin (50μM) reversed the toxic effects of high glucose in HUVECs. These results show that alpha-mangostin, similar to metformin, has anti-senescence effects in high-glucose conditions, which is probably due to its antioxidant activity through the SIRT1 pathway. Alpha-mangostin has previously shown anti-inflammatory effects and metabolic status improvement in animal and clinical studies. Therefore, this natural agent can be considered as a supplement to prevent vascular complications caused by high glucose in patients with diabetes. Graphical abstract.